Both prolactin and estrogen are essential hormones for the growth of 7, 12 dimethylbenzanthracene (DMBA)-induced rat breast cancer and a subphysiological level of the latter is sufficient to stimulate growth. The exact role of these two hormones in tumor growth, the mechanisms of their action, and the mechanisms of their interaction is poorly understood. The aim of this proposal is to provide information in these areas. A working hypothesis is presented to investigate the mechanism of interaction of these two hormones: the regulatory process of one hormone on the receptor sites of the other hormone. This hypothesis is based on the preliminary results in this laboratory that prolactin stimulates estrogen binding capacity in DMBA-tumors both by organ culture and in vivo experiments, and in vivo results having been confirmed by Vignon and Rochefort in France. The relationship of tumor growth to estrogen receptor, and prolactin receptor to changes in hormonal environment will be investigated. Other hormones and biochemicals which are known to stimulate or inhibit DMBA-tumor growth will be investigated as well in an attempt to elucidate the possible pathway of this prolactin and estrogen effect. If this investigation is successful, it will present a prototype for future investigations on the mechanism of peptide-steroid interaction in other systems and will lead to a better understanding of host-tumor inter-relationships.